Multicenter Study Differentiated Thyroid Carcinoma (MSDS)

Summary

Aim: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997). Methods: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msdsstudie.uni-muenster.de). Results: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial’s inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx).

Advised by the trial’s independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (intention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nationwide PCES study underwent RTx in 1996 (p <0.001, χ²-test). Conclusions: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity.

Zusammenfassung

Ziel: Die Multizentrische Studie Differenziertes Schilddrüsenkarzinom (MSDS) ist eine laufende Studie in Deutschland, Österreich und der Schweiz zum klinischen Nutzen der adjuvanten perkutanen Strahlentherapie (RTx) bei lokal invasivem differenziertem Schilddrüsenkarzinom (DTC) in den TNM-Stadien pT4 pN0/1/x M0/x (5. Aufl.1997). Methoden: MSDS war als randomisierte Studie geplant. Die Therapie umfasst Thyreoidektomie, ablative Radioiodtherapie (RIT) und TSHSuppressionstherapie mit oder ohne RTx nach dokumentierter Elimination des zervikalen Iod-131-Uptakes (http://msds-studie.uni-muenster.de). Ergebnisse: 311 Patienten wurden zwischen Januar 2002 und März 2003 gemeldet. 279 Patienten erfüllten die Einschlusskriterien. 45 stimmten der Randomisierung zu. 17 wurden in den Arm A (RTx) und 18 in Arm B (keine RTx) randomisiert. In Abstimmung mit dem unabhängigen Data Monitoring and Safety Committee beschloss das MSDS-Protokollkomitee im April 2003, die Randomisie-rung zu beenden. Von 234 Patienten im Beobachtungsarm wurden 23 dem RTx-Arm zugewiesen. Somit wurden 14% der MSDS-Kohorte per Randomisierung oder Zuweisung der RTx zugeteilt. Hingegen erhielten 1996 44% aller Patienten mit papillärem DTC pT4 in Deutsch-land RTx (PCES-Studie; p <0.001, χ²-Test). Schlussfolgerung: Die Akzeptanz der RTx zur Behandlung des DTC ist so weit zurückgegangen, dass die Rekrutierung einer ausreichenden Zahl von Patienten für eine randomisierte Studie nicht möglich ist. Die Beobachtung der MSDS-Kohorte wird fortgesetzt, um die Rezidivraten mit und ohne RTx und die chronische Toxizität nach RTx zu erfassen.

Keywords

Thyroid carcinoma - radiotherapy - randomized trial - radio-iodine - thyroidectomy

Schlüsselwörter

Schilddrüsenkarzinom - Strahlentherapie - randomisierte Studie - Radioiod - Thyreoidektomie

^# MSDS group

^# Study chairman: Prof. Dr. Dr.O. Schober.* Vice chairman: Prof. Dr. N.Willich.* Study co-ordinators: Dr. M. Biermann,* Dr. Michaela K. Pixberg. Reference centers: Biometrics: Dr. A. Heinecke,* Prof. Dr.W. Köpcke.* Pathology: Prof. Dr.W. Böcker* (Münster), Prof. Dr. Gabriele Köhler (Münster), Prof. Dr. C. Poremba (Düsseldorf), Prof. Dr. K.W. Schmid*. Surgery: Prof. Dr. H. Dralle,* Prof. Dr. N. Senninger (Münster),* Dr. M. Colombo-Benkmann (Münster). Radiotherapy: PD Dr.A. Schuck,* Prof.Dr.N.Willich.* Radiotherapy advisory panel: Prof.Dr.Willich* (chairman), Prof.Dr.Dr. Kimmig (Kiel), Prof. Dr. Marie-Luise Sautter-Bihl (Karlsruhe), Prof. Sauerwein (Essen), PD Dr. A. Schuck*, Prof. Dr. Seegenschmiedt (Essen). Clinical monitoring: Prof. Dr. Chr. Reiners,* Dr. M. Geling (Würzburg). Independent Data Monitoring and Safety Committee: Prof. Dr. H.W. Hense (Münster; chairman), Prof. Dr. H. Jürgens,* Prof. Dr. L. Kiesel (Münster), PD Dr. P.-A. Löschmann (Münster). Members of the MSDS steering committee are indicated by an asterisk (*). MSDS study participants (nuclear medicine; number of patients recruited until 15 Sept 2003 in parentheses): O. Schober, Christiane Franzius, M.Weckesser, Münster (41); H. Schicha, M. Dietlein, C. Kobe, Köln (39); H. Bihl,U. Dörr, Stuttgart (28); H. Lerch, H. Schlemmer,Wuppertal (24);Traute Mende, Jana Grimm, Halle (22); C. Kirsch, C.Alexander,U. Nestle, Homburg/Saar (16); C. Reiners, S. Ladner, Würzburg (14); R. Bauer, Semira Sepehr-Rezai, Nicole Bena-Boupda, Dagmar Steiner, Gießen (10); E. Moser, T. Zajic, Freiburg (9); A. Bockisch, Sandra Rosenbaum, R. Görges, Essen (8); M. Schwaiger,G. Meisetschläger, K. Scheidhauer, München (8); H. Otto, Peggy Fostitsch, R. Steinke, Magdeburg (8);W. Knapp, J. Müller, Daniela Paral, Eva Weckesser, Hannover (8); F. Maul, Cornelia Puskás, J. Peter, Karlsruhe (7); P. Lind, Gerhild Kumnig, Klagenfurt (7); H. Wieler, Elisabeth Ostwald-Lenz, Birthe Müller, Koblenz (7); B.Theophil, J. Borkopp, Gerlinde Thiemann, Dortmund (7); R. Dudczak, A. Becherer,Wien (7); P. Bartenstein, Waltraud Eichhorn, Mainz (7); B. Piotrowski, B. Hackmann, Hamm (6); C. Schümichen, P. Groth, Rostock (5); F. Gottschalk, Frankfurt/O. (5);T.Kuwert, E. Fiedler,A. Schwarz, Erlangen (4);G. von Schulthess, H. Steinert, Zürich (4); R. Schöneich, Gabriele Holl, Potsdam (4);W. Langsteger, Elfriede Rechberger, Linz (4); H. Müller-Gärtner, K. Kley, Düsseldorf (3);G. Klaushenke, Angelika Deutschmann, Oldenburg (3); P. Lindner, A. Glasow, Hildesheim (3);O. Sabri, P. Georgi, L. Otto, Leipzig (3); C. Eilles, A. Szikszai, Regensburg (3); J. Feldkamp, J. Herrmann, Nicole Mittemeyer,G. Frese, Bielefeld (3); M. Clausen, Vika Müller, Hamburg (3);M.Schmidt, R. Nastvogel, H. Philipp, Bamberg (2); R. Baum,M.Schmücking, Bad Berka (2); Ch. Dschietzig, Katrin Weigel, Cottbus (2); H. Biersack, K. von Mallek, Bonn (1);Wilhelmine Maschek, Elisabeth Dienstl, H. Huber, Linz (1); R.Aurisch, M.Tosch, Mönchengladbach (1); R. Thiele, Schwäbisch Hall (1); M. Bähre, E. Richter, Isabel Lauer, Lübeck (1); E. Bell, M. Fischer, Dernbach (1); K. Hering, H. I. Lux, H.Tonscheid, Dortmund (1);U. Haberkorn, J. Hoffend, S. Haufe, Heidelberg (1); K. Hahn, M. Hacker, P. Knesewitsch, München (1).

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